Bayesian graphical network analyses reveal complex biological interactions specific to Alzheimer's disease

Alan Rembach, Francesco C. Stingo, Christine Peterson, Marina Vannucci, Kim Anh Do, William J. Wilson, S. Lance Macaulay, Timothy M. Ryan, Ralph N. Martins, David Ames, Colin L. Masters, James D. Doecke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

With different approaches to finding prognostic or diagnostic biomarkers for Alzheimer's disease (AD), many studies pursue only brief lists of biomarkers or disease specific pathways, potentially dismissing information from groups of correlated biomarkers. Using a novel Bayesian graphical network method, with data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the aim of this study was to assess the biological connectivity between AD associated blood-based proteins. Briefly, three groups of protein markers (18, 37, and 48 proteins, respectively) were assessed for the posterior probability of biological connection both within and between clinical classifications. Clinical classification was defined in four groups: high performance healthy controls (hpHC), healthy controls (HC), participants with mild cognitive impairment (MCI), and participants with AD. Using the smaller group of proteins, posterior probabilities of network similarity between clinical classifications were very high, indicating no difference in biological connections between groups. Increasing the number of proteins increased the capacity to separate both hpHC and HC apart from the AD group (0 for complete separation, 1 for complete similarity), with posterior probabilities shifting from 0.89 for the 18 protein group, through to 0.54 for the 37 protein group, and finally 0.28 for the 48 protein group. Using this approach, we identified beta-2 microglobulin (β2M) as a potential master regulator of multiple proteins across all classifications, demonstrating that this approach can be used across many data sets to identify novel insights into diseases like AD.

Original languageEnglish
Pages (from-to)917-925
Number of pages9
JournalJournal of Alzheimer's Disease
Volume44
Issue number3
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Bayesian
  • biomarkers
  • graphical networks
  • imputation

Fingerprint

Dive into the research topics of 'Bayesian graphical network analyses reveal complex biological interactions specific to Alzheimer's disease'. Together they form a unique fingerprint.

Cite this